Our objective is a generalized understanding of the mechanisms by which oxygen supports life, in terms of the structures of oxidases, oxygen, and substrates, and the mechanisms of oxygen-activating enzymic reactions. We propose to investigate selected dioxygenases, mixed function oxidases, and electron transfer oxidases, primarily those with copper, iron (non-heme) or heme as prosthetic groups. We propose to continue our biochemical and biophysical studies by (1) determining the structures of active sites and the related protein structures of copper and heme oxidases; (2) characterizing the reactions which take place at the active sites of these oxidases with oxygen and substrates, and reducing cofactors if any; (3) attempting to observe the metastable and reactive forms of the enzymes by seeking new techniques for forming, detecting, and characterizing functional enzyme complexes of oxygen and substrates. We propose to formalize our generalized understanding of oxidase structure and mechanism. We propose also to undertake an exploration of the metabolic consequences of hypoxia on the functions of dioxygenases and mixed function oxidases ("metabolic hypoxia").